Monitoring and evaluation of health system reforms are essential to ensure the achievement of their objectives. The latest heath sector reform in the Islamic Republic of Iran, namely, the Health Transformation Plan (HTP), was launched in 2014 and the country is embarking on the HTP to achieve universal health coverage (UHC).The study aimed to develop the most appropriate monitoring and evaluation framework for the HTP in accordance with national and global goals and priorities, and to identify data gaps in its monitoring and evaluation.A case study and evidence-based approach was applied to develop the monitoring and evaluation framework. The model that was proposed jointly by the World Bank and the World Health Organization for monitoring and evaluation of UHC was used as the basis for the potential list of the indicators and key policy documents were reviewed, accordingly. The framework formulation process was carried out through a series of meetings with experts and senior managers working at the Ministry of Health and Medical Education, whose perspectives on the frameworks functionality and usage were regarded as valuable. The final draft was presented to policy-makers for input and approval.A data mapping revealed that at least nine national surveys were required to obtain the indicators for effective monitoring. At the time of framework designing, many indicators were not available or had not been updated for several years due to lack of available and appropriate data sources.Results indicated that the country's health information system had many information gaps that should be filled to enable the tracking of UHC goals and measuring the success of the plan. Applying the proposed framework would increase the comparability of the country's health indicators at the global level and specify a path to successfully achieve the objectives of the reform.